Neuroinflammation and kynurenines in schizophrenia: Impact on cognition depending on cognitive functioning and modulatory properties in relation to cognitive remediation and aerobic exercise.

Autor:	Sapienza J; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Department of Humanities and Life Sciences, University School for Advanced Studies IUSS, Pavia, Italy., Agostoni G; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Comai S; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.; Division of Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Department of Psychiatry, McGill University, Montreal, QC, Canada.; Department of Biomedical Sciences, University of Padua, Padua, Italy., Nasini S; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy., Dall'Acqua S; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy., Sut S; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy., Spangaro M; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Martini F; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Bechi M; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Buonocore M; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Bigai G; School of Medicine, Vita -Salute San Raffaele University, Milan, Italy., Repaci F; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Nocera D; School of Medicine, Vita -Salute San Raffaele University, Milan, Italy., Ave C; School of Medicine, Vita -Salute San Raffaele University, Milan, Italy., Guglielmino C; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Cocchi F; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy., Cavallaro R; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.; School of Medicine, Vita -Salute San Raffaele University, Milan, Italy., Deste G; Department of Mental Health, Spedali Civili Hospital, Brescia, Italy., Bosia M; Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.; School of Medicine, Vita -Salute San Raffaele University, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Schizophrenia research. Cognition [Schizophr Res Cogn] 2024 Aug 29; Vol. 38, pp. 100328. Date of Electronic Publication: 2024 Aug 29 (Print Publication: 2024).
DOI:	10.1016/j.scog.2024.100328
Abstrakt:	Background: In the last decade, the kynurenine pathway (KP) has gained attention in the pathogenesis of cognitive impairment in schizophrenia being at the croassroad between neuroinflammation and glutamatergic and cholinergic neurotransmission. However, clinical findings are scarse and conflicting, and the specific contributions of these two systems to the neurobiology of cognitive symptoms are far from being elucidated. Furthermore, little is known about the molecular underpinnings of non-pharmacological interventions for cognitive improvement, including rehabilitation strategies. Methods: The current study examined 72 patients with schizophrenia, divided in two clusters depending on the severity of the cognitive impairment, with the aim to evaluate the impact of inflammatory biomarkers and KP metabolites depending on cognitive functioning. Moreover, we studied their possible link to the cognitive outcome in relation to sessions of cognitive remediation therapy (CRT) and aerobic exercise (AE) in a longitudinal arm of 42 patients. Results: Neuroinflammation appeared to exert a more pronounced influence on cognition in patients exhibiting a higher cognitive functioning, contrasting with the activation of the KP, which had a greater impact on individuals with a lower cognitive profile. Cognitive improvements after the treatments were negatively predicted by levels of TNF-α and positively predicted by the 3-hydroxykynurenine (3-HK)/kynurenine (KYN) ratio, an index of the kynurenine-3-monooxygenase (KMO) enzyme activity. Conclusion: Overall, these findings add novel evidence on the biological underpinnings of cognitive impairment in schizophrenia pointing at a differential role of neuroinflammation and KP metabolites in inducing cognitive deficits depending on the cognitive reserve and predicting outcomes after rehabilitation. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 Published by Elsevier Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu